Effect of Mutations in T2DM Susceptibility Genes on the Expression of Susceptibility Genes in Patients With T2DM and Controls

Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical University

In this study, investigators wanted to determine the effect of T2DM susceptibility gene mutations on self-expression.

Participants (T2DM patients and controls) were recruited to identify genotypes and detect the levels of T2DM susceptibility genes expression in the fresh peripheral plasma. The normal pancreatic tissues or adjacent tissues of pancreatic cancer were also collected to identify the expression differences of T2DM susceptibility genes under different genotypes.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus; Genetic Mutations; Gene Polymorphisms; Susceptibility, Genetic
• Intervention / Treatment: Drug: Fresh normal pancreatic tissues or adjacent tissues of pancreatic cancer were collected from controls and T2DM patients without hypoglycemic drugs; Drug: Fresh blood samples were collected from healthy subjects and T2DM patients without hypoglycemic drugs

Detailed Description

The primary objective of this study was to investigate the changes of the expression of T2DM susceptible genes (NOS1AP, KCNQ1, TCF7L2, WSF1, GLP-1R, etc.) in participants (newly diagnosed T2DM patients and controls) after gene mutation.

Secondly, the expression differences of T2DM susceptible genes in T2DM patients with different genotypes were compared, and the relationship between the expression differences and clinicopathological characteristics of T2DM patients was analyzed.

Participants (newly diagnosed T2DM patients and healthy subjects) were screened from the department of endocrinology and health management center, whose fresh peripheral blood were collected. The normal pancreatic tissues or adjacent tissues of pancreatic cancer were collected in the department of general surgery. The DNA genome was extracted for genotyping, and then the expression levels of T2DM related susceptibility genes under different genotypes were detected by ELISA kits, PCR, WB,HE staining, IHC staining, ect.

The basic information of T2DM patients was collected, including demographic characteristics, physiological and biochemical data.Then investigators further compared the differences in the expression of susceptible genes between newly diagnosed T2DM patients and controls.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tao Wang, Ph.D; Phone Number: 13815344640; Email: misswt2011@126.com
• Study Contact Backup: Name: Xiaoxing Yin, Ph.D; Phone Number: 13605218523; Email: yinxx@xzmc.edu.cn

Study Locations

• China
  • Xuzhou, China, 221006
    • Recruiting
    • China, Jiangsu, Department of Endocrinology
    • Contact: Hongwei Ling, MD; Phone Number: 18052268607; Email: linghongwei@medmail.com.cn
    • Principal Investigator: Renguo Chen, MD
    • Sub-Investigator: Yuhan Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. no drug therapy; 25 to 70 years old; Hemoglobin A1c (HbA1c) 7%-12%; BMI 20-35 kg/m2; Stable body weight (≤10% change within 3 months)（For newly diagnosed patients with T2DM）.
2. 25 to 60 years old; BMI 19-26 kg/m2; in good health, with no abnormalities of motor system, digestive system, respiratory system, urogenital system, blood system, circulatory system, nervous/mental system, endocrine system, etc（For healthy subjects）.
3. 20-80 years old; surgical resection of part or all of the pancreas; pancreatic lesions confirmed by enhanced CT or magnetic resonance (MR) examination or confirmed by intraoperative and postoperative pathology（For the patients in general surgical）.

Exclusion Criteria:

1. had taken antidiabetic drugs;
2. had a history of pancreatic surgery;
3. Complicated with severe organ lesions;
4. Long-term use of drugs that affect pancreatic function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Comparison of T2DM susceptibility gene expression between newly diagnosed T2DM patients and controls; To determine the effect of gene mutations on the susceptibility of T2DM by comparing the expression levels of T2DM susceptibility genes in newly diagnosed T2DM patients and controls.

Drug: Fresh normal pancreatic tissues or adjacent tissues of pancreatic cancer were collected from controls and T2DM patients without hypoglycemic drugs; Compared with newly diagnosed T2DM patients, healthy subjects in the control group had normal levels of blood glucose, lipids, glycated hemoglobin levels, etc. Fresh normal pancreatic tissues or adjacent tissues of pancreatic cancer were collected before taking antidiabetic drugs in both groups.; Drug: Fresh blood samples were collected from healthy subjects and T2DM patients without hypoglycemic drugs; The newly diagnosed T2DM group should not have taken antidiabetic drugs and meet the diagnosis of T2DM. Fresh blood samples were collected before medication for detection. In the control group (healthy subjects), the indicators of physical examination were within the normal range and no hypoglycemic drugs were taken. Similarly, fresh blood samples should be taken for testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of T2DM susceptibility gene expression in newly diagnosed T2DM patients	To detect the expression levels of susceptible genes in the plasma and the pancreatic tissues of newly diagnosed T2DM patients and compared with those in healthy subjects.	1 month after fresh sample collection
Detection of T2DM susceptibility gene expression in controls	To detect the expression levels of susceptible genes in the plasma and the pancreatic tissues of controls and compared with those in newly diagnosed T2DM patients.	1 month after fresh sample collection
Correlation between T2DM susceptibility gene expression and clinicopathological features	Incidence of clinical pancreatic diseases under expression differences in T2DM susceptibility genes	6 months after obtaining the clinicopathological results

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline BMI of newly diagnosed with T2DM patients with different genotypes	Baseline BMI of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline HbA1c of newly diagnosed with T2DM patients with different genotypes	Baseline HbA1c of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline TC of newly diagnosed with T2DM patients with different genotypes	Baseline TC of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline TG of newly diagnosed with T2DM patients with different genotypes	Baseline TG of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline HDL-C of newly diagnosed with T2DM patients with different genotypes	Baseline HDL-C of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline LDL-C of newly diagnosed with T2DM patients with different genotypes	Baseline LDL-C of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline BMI of controls with different genotypes	Baseline BMI of controls	1 month of completion for individual screening
Baseline WHR of controls with different genotypes	Baseline WHR of controls	1 month of completion for individual screening
Baseline FPG of controls with different genotypes	Baseline FPG of controls	1 month of completion for individual screening
Baseline HbA1c of controls with different genotypes	Baseline HbA1c of controls	1 month of completion for individual screening
Baseline TC of controls with different genotypes	Baseline TC of controls	1 month of completion for individual screening
Baseline TG of controls with different genotypes	Baseline TG of controls	1 month of completion for individual screening
Baseline HDL-C of controls with different genotypes	Baseline HDL-C of controls	1 month of completion for individual screening
Baseline LDL-C of controls with different genotypes	Baseline LDL-C of controls	1 month of completion for individual screening
Baseline waist hip ratio (WHR) of newly diagnosed with T2DM patients with different genotypes	Baseline WHR of newly diagnosed with T2DM patients	1 month of completion for individual screening
Baseline fasting plasma glucose (FPG) of newly diagnosed with T2DM patients with different genotypes	Baseline FPG of newly diagnosed with T2DM patients	1 month of completion for individual screening

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 18, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 25, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: T2DM; gene polymorphism; genetic mutations; susceptibility gene
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease Attributes; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Susceptibility; Genetic Predisposition to Disease; Physiological Effects of Drugs; Hypoglycemic Agents
• Other Study ID Numbers: XYFY2023-KL478-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No